This application requests funding to purchase a JOEL JEM-1010 transmission electron microscope, digital image acquisition system, and high resolution printer for the University of Pennsylvania Medical Center (UPMC) and the Electron Microscopy Core Facility which is supported by the Institution, the Diabetes and Endocrinology Research Center (DERC) and Cancer Center. The instrument will replace a JOEL 100CX microscope installed 17 years ago in the Core Facility which has been used for ultrastructural studies for over 50 NIH-supported investigators resulting in over 200 publications. This application identifies 17 NIH-supported investigators at UPMC and elsewhere as the Major User Group(MUG). It is estimated an additional 8- 12 investigators per year with less extensive projects also will benefit directly from the purchase of this instrument. The existing microscope is in actual use almost 40 hr per week. The heavy usage has resulted in predictable and unpreventable deterioration of some mechanical systems. Down-time has increased and become unacceptable, primarily because replacement parts for key systems, e.g., the camera mechanism, knobs, etc., have to be fabricated, rebuilt, or scavenged from discarded instruments. The new instrument will be operated by an experienced professional and technical staff for the MUG or others trained by them. Utilization of the instrument and the operational of the Core Facility are controlled by the Institution's Core Research Facilities Committee and an Advisory Committee composed of investigators from the MUG and supporting Centers. The new instrument, with its advancements in electron optics, and the digital camera system will enhance our ability to provide and communicate state-of-the-art ultrastructural analyses to investigators of the MUG at a lower cost than commercial firms. The past utilization of the Core Facility and the documentation provided in this application demonstrate this instrument will significantly benefit NIH-supported research at this Institution and elsewhere. The application is supported by the Institutional Research Core Facilities Committee, DERC, and Cancer Center.